Eukaryotic protein translation iniation factor 5A (eIF-5A) contains one residue of hypusine and appears to be the only cellular protein with this unique amino acid. Hypusine is produced post-translationally by transfer of the butylamine portion of the polyamine spermidine to a lysine residue in the eIF-5A precursor to form deoxyhypusine followed by hydroxylation to form hypusine. These findings reveal a novel cellular metabolic pathway. Hypusine is essential for the biological activity of eIF-5A in an in vitro translation initiation assay and hypusine and eIF- 5A appear to be vital elements for growth of eukaryotic cells. Thus, the hypusine biosynthetic steps, deoxyhypusine synthesis and deoxyhypusine hydroxylation present special potential targets for intervention in cellular proliferation. Several inhibitors of the enzymes deoxyhypusine synthase, and deoxyhypusine hydroxylase were developed and their cellular effects have been examined. Studies are underway to relate the structure of hypusine to the physiological function of eIF-5A in mammalian cells.